# FOLFIRI (5-FU, leucovorin, irinotecan)

Source: https://onco.cc/drugs/folfiri/  
OnCo record `folfiri` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

FOLFIRI is the other backbone bowel-cancer chemotherapy, swapping oxaliplatin for irinotecan. Used first or second line and, since 2026, with the BRAF combination.

## Summary

FOLFIRI pairs irinotecan, whose active metabolite SN-38 inhibits topoisomerase I, with 5-FU and leucovorin, which inhibit thymidylate synthase, given as a 46-hour infusion every 14 days. It is one of the two backbone chemotherapies for metastatic colorectal cancer, interchangeable with FOLFOX in first-line efficacy (Tournigand 2004) and the standard second-line switch. It is the partner for cetuximab (CRYSTAL, FIRE-3), bevacizumab, aflibercept, ramucirumab and, since 2026, encorafenib plus cetuximab in BRAF V600E disease (BREAKWATER cohort 3, PFS HR 0.44). Diarrhoea, neutropenia and alopecia are the main toxicities, and UGT1A1*28 homozygotes need irinotecan dose reduction. Whether to start with FOLFIRI or FOLFOX is decided by side-effect preference rather than efficacy. For a newcomer, FOLFIRI is bowel cancer chemotherapy with irinotecan instead of oxaliplatin.

## Fields

- Kind: Treatment
- Status: standard-of-care
- Last checked: 2026-09-07
- Modality: Cytotoxic regimen
- Mechanism: Irinotecan (via SN-38) inhibits topoisomerase I; 5-FU/leucovorin inhibit thymidylate synthase.
- Dosing: Intravenous; Irinotecan 180 mg/m² + leucovorin 400 mg/m² day 1, 5-FU 400 mg/m² bolus then 2,400 mg/m² over 46 h, every 14 days

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/FOLFIRI
- Wikipedia: https://en.wikipedia.org/wiki/FOLFIRI

## Connected records

- drugs: [FOLFOX (5-FU, leucovorin, oxaliplatin)](https://onco.cc/drugs/folfox/), [Ziv-aflibercept](https://onco.cc/drugs/ziv-aflibercept/)
- cancers: [Advanced and metastatic small bowel adenocarcinoma](https://onco.cc/cancers/advanced-small-bowel-adenocarcinoma/), [Appendiceal adenocarcinoma (mucinous and non-mucinous, including signet ring cell)](https://onco.cc/cancers/appendiceal-adenocarcinoma/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Extrapulmonary neuroendocrine carcinoma](https://onco.cc/cancers/extrapulmonary-nec/), [Goblet cell adenocarcinoma of the appendix](https://onco.cc/cancers/goblet-cell-adenocarcinoma/), [HER2-amplified colorectal cancer](https://onco.cc/cancers/her2-amplified-colorectal/), [KRAS G12C-mutant colorectal cancer](https://onco.cc/cancers/kras-g12c-colorectal/), [Rectal cancer](https://onco.cc/cancers/rectal-cancer/), [Small intestine cancer (small bowel adenocarcinoma)](https://onco.cc/cancers/small-bowel/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [St John's wort: an interaction to avoid](https://onco.cc/technologies/st-johns-wort-interaction/), [Topoisomerase-I inhibitors (and ADC payloads)](https://onco.cc/technologies/topoisomerase-inhibitors/)
- trials: [5FU/LV, Irinotecan, Temozolomide and Bevacizumab for MGMT Silenced, Microsatellite Stable Metastatic Colorectal Cancer.](https://onco.cc/trials/nct04689347/), [A Clinical Study of Liposomal Irinotecan for Second-Line Therapy in Metastatic Colorectal Cancer](https://onco.cc/trials/nct07585279/), [A Phase Ib/II Clinical Study on AK112 Combined or Not Combined With AK119 in pMMR/MSS Colorectal Cancer](https://onco.cc/trials/nct05846867/), [A Phase II Study of AMT-676 Combination Therapies in Advanced Colorectal Cancer](https://onco.cc/trials/nct07474727/), [A Single-arm, Single-center, Phase II Clinical Study of Aipalolitovorelizumab (QL1706) Combined With Bevacizumab and Standard Chemotherapy as First-line Treatme](https://onco.cc/trials/nct07229846/), [A Study of a Selective T Cell Receptor (TCR) Targeting, Bifunctional Antibody-fusion Molecule STAR0602 in Participants With Advanced Solid Tumors](https://onco.cc/trials/nct05592626/), [A Study of AK112 With or Without AK117 in Metastatic Colorectal Cancer](https://onco.cc/trials/nct05382442/), [A Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer](https://onco.cc/trials/nct05379595/), [A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors](https://onco.cc/trials/nct04657068/), [A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors](https://onco.cc/trials/nct03526835/), [A Study of Fruquintinib Plus FOLFIRI as Second-Line Treatment for Participants With Metastatic Colorectal Cancer (FRUITFUL)](https://onco.cc/trials/nct07011576/), [A Study of GFH276 Combined With Cetuximab or Chemotherapy in Participants With Solid Tumors and Pancreatic Ductal Adenocarcinoma (PDAC) Harboring RAS Mutation](https://onco.cc/trials/nct07678593/), [A Study of Novel Study Interventions and Combinations in Participants With Colorectal Cancer](https://onco.cc/trials/nct06792695/), [A Study to Evaluate Sacituzumab Tirumotecan (MK-2870) in Advanced/Metastatic Gastroesophageal Adenocarcinoma (MK-2870-015)](https://onco.cc/trials/nct06356311/), [A Study to Evaluate the Safety and Efficacy of Pumitamig in Combination With Chemotherapy Versus Bevacizumab in Combination With Chemotherapy in Parti](https://onco.cc/trials/nct07221357/), [A Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of LRK-4189 Alone and in Combination in Patients With Solid Tumors](https://onco.cc/trials/nct07498725/), [Abemaciclib Combined With FOLFOX/FOLFIRI Regimen in Patients With Advanced Colorectal Liver Metastases Cancer](https://onco.cc/trials/nct07441369/), [AK112 Plus FOLFIRI Versus Bevacizumab Plus FOLFIRI as Second-line Treatment of MSS/pMMR Metastatic Colorectal Cancer](https://onco.cc/trials/nct07021950/), [An Adaptive-design Prospective Cohort Study of Watch and Wait Strategy in Patients With Locally Advanced Rectal Cancer](https://onco.cc/trials/nct04443543/), [Assessing a Regorafenib-irinotecan Combination Versus Regorafenib Alone in Metastatic Colorectal Cancer Patients](https://onco.cc/trials/nct03829462/), [AZD0901 in Participants With Advanced Solid Tumours Expressing Claudin18.2](https://onco.cc/trials/nct06219941/), [BEACON CRC](https://onco.cc/trials/beacon-crc/), [Bevacizumab, Sintilimab, Cetuximab and Irinotecan in Refractory RAS Wild-type Metastatic Colorectal Cancer: BOND-4 Trial](https://onco.cc/trials/nct07722754/), [BREAKWATER](https://onco.cc/trials/breakwater/), [CAIRO5](https://onco.cc/trials/cairo5/), [CALGB/SWOG 80405](https://onco.cc/trials/calgb-80405/), [Cetuximab Plus Irinotecan in Patients With NeoRAS Wild-type Metastatic Colorectal Cancer In Third-line Therapy](https://onco.cc/trials/nct05962502/), [Cetuximab, Irinotecan, Toripalimab in RAS/BRAF Wild-type Ultraselected Right-sided Colorectal Cancer Study](https://onco.cc/trials/nct06547203/), [CGA Guided Ultrafractionated RT and Systemic Treatment in Elderly or Frail Patients with Inoperable Localized CRC](https://onco.cc/trials/nct06652412/), [Continuation of Cetuximab Beyond First-Line Progression in Metastatic Colorectal Cancer](https://onco.cc/trials/nct07389265/), [CRYSTAL & FIRE-3](https://onco.cc/trials/crystal-fire3/), [DCE-MRI for Neoadjuvant Treatment Assessment in Patients With Borderline Resectable Pancreatic Cancer](https://onco.cc/trials/nct07705919/), [Dual EGFR/HER2 Blockade Combined With Irinotecan for the Treatment of HER2-Positive Metastatic Colorectal Cancer](https://onco.cc/trials/nct07059338/), [Efficacy of Hyperthermic Intraperitoneal Chemotherapy](https://onco.cc/trials/nct04861558/), [FOLFIRI and Bevacizumab With or Without Pelareorep for Second-Line Treatment of Metastatic RAS-Mutated, Microsatellite-Stable Colorectal Cancer](https://onco.cc/trials/nct07446322/), [FOLFOX Via HAI Plus Intravenous Irinotecan With or Without Bevacizumab Versus Systemic FOLFOXIRI With or Without Bevacizumab in Initially Unresectable RAS-mutat](https://onco.cc/trials/nct05727163/), [FOLFOXIRI Plus Bevacizumab With or Without Atezolizumab as 1st Line Treatment of pMMR and IS IC-High Metastatic Colorectal Cancer Patients.](https://onco.cc/trials/nct06733038/), [Gemcitabine Plus Nab-paclitaxel as Switch Maintenance Versus Continuation of Modified FOLFIRINOX as 1st Line Chemotherapy in Patients With Advanced Pancreatic C](https://onco.cc/trials/nct06897644/), [HSK42360-Na Tablets Combined With Cetuximab With or Without Chemotherapy in BRAF V600-Mutant Metastatic Colorectal Cancer](https://onco.cc/trials/nct07790510/), [Hypofractionated Radiotherapy Plus Immunotherapy Versus Conventional Radiotherapy in Locally Recurrent Rectal Cancer](https://onco.cc/trials/nct06928584/), [Intermittent or Continuous Panitumumab Plus FOLFIRI for Left Sided RAS/B-RAF Wild-type Metastatic Colorectal Cancer](https://onco.cc/trials/nct06509126/), [LPM6690176 in Combination With Chemotherapy and Bevacizumab in Metastatic Colorectal Cancer Patients With RAS Mutation](https://onco.cc/trials/nct07391566/), [Lurbinectedin or in Combination with Irinotecan Versus Topotecan in Patients with Relapsed SCLC](https://onco.cc/trials/nct06496048/), [mFOLFOX/mFOLFIRI vs. mFOLFOX in Advanced or Recurrent Biliary Tract Cancer Second-line](https://onco.cc/trials/nct07062536/), [MNK Inhibitor AUM001 in Combination With Either Pembrolizumab or Irinotecan to Treat Metastatic Colorectal Cancer](https://onco.cc/trials/nct05462236/), [NC410 and FOLFIRINOX in Combination With Nivolumab With or Without Ipilimumab in Patients With Untreated Metastatic Pancreatic Cancer](https://onco.cc/trials/nct06941857/), [Oncolytic Virus (H101) + SBRT + Chemotherapy + Targeted Therapy + Immunotherapy for Unresectable CRLM](https://onco.cc/trials/nct07381309/), [Pegcetacoplan in Combination With Modified FOLFIRINOX for the Treatment of Metastatic Pancreatic Ductal Adenocarcinoma](https://onco.cc/trials/nct07214298/), [Phase 1/2 Trial of S241656 in Selected RAS/MAPK Mutation- Positive Malignancies](https://onco.cc/trials/nct05786924/), [Post-resection/Ablation Chemotherapy in Patients With Metastatic Colorectal Cancer (FIRE-9 - PORT / AIO-KRK-0418)](https://onco.cc/trials/nct05008809/), [Preoperative Chemoradiotherapy and Toripalimab in Locally Recurrent Rectal Cancer](https://onco.cc/trials/nct06751394/), [RAISE](https://onco.cc/trials/raise/), [ROMANCE: "Irinotecan Plus Cetuximab Rechallenge Versus Trifluridine/Tipiracil Plus Bevacizumab in Molecularly Selected Metastatic Colorectal Cancer"](https://onco.cc/trials/nct07381764/), [Safety and Efficacy of IB-FOLFIRI in BRAF V600E-Mutant Metastatic Colorectal Cancer](https://onco.cc/trials/nct07150247/), [Second-line Doublet Chemotherapy (FOLFOX or FOLFIRI) Plus Fruquintinib Versus Doublet Chemotherapy (FOLFOX or FOLFIRI) Plus Bevacizumab in Metastatic Colorectal](https://onco.cc/trials/nct07150403/), [Second-line Zimberelimab and SIRIOX Chemotherapy for Patient With Previously AG Chemotherapy Treated Pancreatic Cancer](https://onco.cc/trials/nct06166589/), [SMAD4 Tailored Neoadjuvant Therapy for the Treatment of Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma, SMART-PANC Trial](https://onco.cc/trials/nct07748611/), [Small Cell Lung Cancer Irinotecan and CDC2-like Kinase Inhibition Trial (SLICK Trial)](https://onco.cc/trials/nct07155200/), [Study in mCRC Patients RAS/BRAF wt Tissue and RAS Mutated LIquid BIopsy to Compare FOLFIRI Plus CetuxiMAb or BevacizumaB](https://onco.cc/trials/nct04776655/), [Study of Onvansertib in Combination With FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab Versus FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab fo](https://onco.cc/trials/nct06106308/), [Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors](https://onco.cc/trials/nct03709680/), [Study of Petosemtamab Plus Chemotherapy Versus Cetuximab Plus Chemotherapy in RAS and BRAF Wild-type, Unresectable or Metastatic, Left-sided Colorecta](https://onco.cc/trials/nct07702032/), [Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-muta](https://onco.cc/trials/nct07621718/), [Study to Assess Adverse Events and Change in Disease Activity in Previously Treated Adult Participants Receiving Intravenous (IV) ABBV-400 With Unrese](https://onco.cc/trials/nct06107413/), [Studying Chemotherapy With or Without Panitumumab for Unresectable, Locally Advanced, or Metastatic Pancreatic Cancer Without KRAS Mutations](https://onco.cc/trials/nct06998940/), [Systemic Oxaliplatin or Intra-arterial Chemotherapy Combined With LV5FU2 +/- Irinotecan and an Target Therapy in First Line Treatment of Metastatic Colorectal C](https://onco.cc/trials/nct02885753/), [Testing the Addition of an Anti-Cancer Drug, Irinotecan, to the Standard Chemotherapy Treatment (FOLFOX) After Long-Course Radiation Therapy for Advanced-Stage](https://onco.cc/trials/nct05610163/), [The Combination of Hypofractionated Radiotherapy and Immunotherapy in Locally Recurrent Rectal Cancer](https://onco.cc/trials/nct05628038/), [The Sagittarius Trial](https://onco.cc/trials/nct06490536/), [The Study of JMT101 Combined With Irinotecan as a ≥3rd-Line Treatment in Metastatic Colorectal Cancer](https://onco.cc/trials/nct07134205/), [Tovecimig Plus FOLFIRI in Second Line Metastatic Colorectal Cancer](https://onco.cc/trials/nct07662031/), [TRIBE](https://onco.cc/trials/tribe/), [TRIBE2](https://onco.cc/trials/tribe2/), [ValproIc Acid to Potentiate Anti-EGFR Treatment Efficacy and Prevent/Revert Resistance in Colorectal Cancer](https://onco.cc/trials/nct06714357/), [VELOUR](https://onco.cc/trials/velour/), [Vitamin D3 With Chemotherapy and Bevacizumab in Treating Patients With Advanced or Metastatic Colorectal Cancer](https://onco.cc/trials/nct04094688/)
- pairings: [Anti-EGFR antibody + chemotherapy in left-sided RAS/BRAF wild-type mCRC](https://onco.cc/pairings/anti-egfr-left-sided/)
- key papers: [Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer (CRYSTAL)](https://onco.cc/key-papers/paper-van-cutsem-crystal-cetuximab-folfiri-nejm-2009/), [Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in KRAS wild-type advanced or metastatic colorectal cancer (CALGB/SWOG 80405)](https://onco.cc/key-papers/paper-venook-calgb-80405-cetuximab-vs-bevacizumab-jama-2017/), [Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC)](https://onco.cc/key-papers/paper-kopetz-beacon-encorafenib-braf-colorectal-nejm-2019/), [FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3)](https://onco.cc/key-papers/paper-heinemann-fire-3-cetuximab-vs-bevacizumab-lancet-oncol-2014/), [FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of TRIBE](https://onco.cc/key-papers/paper-cremolini-tribe-folfoxiri-bevacizumab-lancet-oncol-2015/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/)
- terms: [Living with FOLFOX, CAPOX, FOLFIRI and the EGFR antibodies](https://onco.cc/terms/chemotherapy-side-effects-colorectal/)

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