{"entity":{"id":"folfoxiri","kind":"drug","name":"FOLFOXIRI (5-FU, leucovorin, oxaliplatin, irinotecan)","aka":[],"tldr":"All three of the active bowel cancer chemotherapy drugs given together instead of two. It shrinks more tumours than a doublet and is chosen when shrinking the tumour is what matters, usually with bevacizumab.","summary":"FOLFOXIRI combines infusional fluorouracil and leucovorin with both oxaliplatin and irinotecan every fourteen days, most often with bevacizumab. TRIBE showed that FOLFOXIRI plus bevacizumab gives a longer progression-free survival (12.1 against 9.7 months) and a higher response rate (65 against 53 percent) than FOLFIRI plus bevacizumab in untreated metastatic disease, and TRIBE2 showed the advantage survives as a strategy, with progression-free survival 2 of 19.2 against 16.4 months against a planned sequence of doublets. CAIRO5 found it the best induction for right-sided or RAS/BRAF-mutant liver-limited disease. The price is toxicity: grade 3 or 4 neutropenia in about half of patients, and more diarrhoea, stomatitis and neuropathy, so it is reserved for fit patients under about 75 with good performance status. In practice it is used when deep response matters most, to convert unresectable liver metastases, in BRAF V600E disease before the targeted triplet was available, and in young patients with heavy disease burden. Induction is usually limited to eight to twelve cycles followed by fluoropyrimidine and bevacizumab maintenance.","status":"established","asOf":"2026-09-24","links":[{"label":"TRIBE: initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer (New England Journal of Medicine 2014)","url":"https://doi.org/10.1056/NEJMoa1403108"},{"label":"TRIBE2 (Lancet Oncology 2020)","url":"https://doi.org/10.1016/S1470-2045(19)30862-9"},{"label":"NCCN Colon Cancer guideline","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1428"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["cytotoxic-chemotherapy","platinum","topoisomerase-inhibitors"],"targets":["dpyd","ugt1a1"],"drugs":["fluorouracil","leucovorin","oxaliplatin","irinotecan","bevacizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["tribe","tribe2","cairo5"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"mFOLFOXIRI","modality":"Cytotoxic regimen","mechanism":"Oxaliplatin crosslinks DNA, irinotecan (through SN-38) traps topoisomerase I, and fluorouracil with leucovorin inhibits thymidylate synthase: three separate attacks on DNA replication at once.","approvals":[],"mechanismSteps":["Oxaliplatin forms platinum adducts that crosslink the two strands of DNA","Irinotecan is converted to SN-38, which traps topoisomerase I on DNA and causes strand breaks","Fluorouracil, held on the enzyme by leucovorin, starves the cell of thymidine","A dividing cell facing all three cannot repair or replicate and dies"],"dosing":{"route":"Intravenous","schedule":"Irinotecan 165 mg/m2 and oxaliplatin 85 mg/m2 with leucovorin 200 mg/m2 on day 1, then fluorouracil 3,200 mg/m2 as a 48-hour infusion, every 14 days (modified schedules reduce irinotecan to 150 mg/m2 and fluorouracil to 2,400 mg/m2)","modifications":"Dose-reduce for UGT1A1*28 homozygotes and for age over 70; test DPYD before any fluoropyrimidine","monitoring":"Full blood count before each cycle, neuropathy score, early and late diarrhoea"},"toxicity":[{"event":"Neutropenia (grade 3-4)","grade3PlusPct":50,"source":"https://doi.org/10.1016/S1470-2045(19)30862-9","note":"50 percent in the TRIBE2 experimental arm against 21 percent with a doublet"},{"event":"Diarrhoea (grade 3-4)","grade3PlusPct":17,"source":"https://doi.org/10.1016/S1470-2045(19)30862-9"},{"event":"Peripheral sensory neuropathy","note":"Cumulative, from oxaliplatin"},{"event":"Stomatitis"}],"access":[],"regulatoryEvents":[]},"route":"/drugs/folfoxiri/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}],"target":[{"id":"dpyd","kind":"target","name":"DPYD","route":"/targets/dpyd/"},{"id":"ugt1a1","kind":"target","name":"UGT1A1","route":"/targets/ugt1a1/"}],"drug":[{"id":"bevacizumab","kind":"drug","name":"Bevacizumab","route":"/drugs/bevacizumab/"},{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"irinotecan","kind":"drug","name":"Irinotecan (and liposomal irinotecan)","route":"/drugs/irinotecan/"},{"id":"leucovorin","kind":"drug","name":"Leucovorin (folinic acid)","route":"/drugs/leucovorin/"},{"id":"oxaliplatin","kind":"drug","name":"Oxaliplatin","route":"/drugs/oxaliplatin/"}],"trial":[{"id":"nct07229846","kind":"trial","name":"A Single-arm, Single-center, Phase II Clinical Study of Aipalolitovorelizumab (QL1706) Combined With Bevacizumab and Standard Chemotherapy as First-line Treatme","route":"/trials/nct07229846/"},{"id":"nct05427669","kind":"trial","name":"Adjuvant mFOLFOXIRI vs. mFOLFOX6 in MRD Positive Stage II-III Colorectal Cancer (AFFORD)","route":"/trials/nct05427669/"},{"id":"cairo5","kind":"trial","name":"CAIRO5","route":"/trials/cairo5/"},{"id":"nct06242418","kind":"trial","name":"CtDNA in Adjuvant Chemotherapy of Stage III Colon Cancer (REVISE Trial)","route":"/trials/nct06242418/"},{"id":"nct07817888","kind":"trial","name":"mFOLFOXIRI Plus Bevacizumab for Organ Preservation in Locally Advanced Rectal Cancer","route":"/trials/nct07817888/"},{"id":"nct07472868","kind":"trial","name":"Neoadjuvant FOLFOXIRI and Chemoradiotherapy Versus Neoadjuvant CAPOX/FOLFOX and Chemoradiotherapy Followed by Surgery or a Watch-and-Wait Approach in High Risk","route":"/trials/nct07472868/"},{"id":"nct05201430","kind":"trial","name":"Neoadjuvant FOLFOXIRI Versus CapeOX Chemotherapy for Local Advanced Rectal Cancer","route":"/trials/nct05201430/"},{"id":"nct05571644","kind":"trial","name":"Neoadjuvant Treatment With mFOLFOXIRI Plus Cadonilimab (AK104) Versus mFOLFOX6 in Locally Advanced Colorectal Cancer","route":"/trials/nct05571644/"},{"id":"nct05008809","kind":"trial","name":"Post-resection/Ablation Chemotherapy in Patients With Metastatic Colorectal Cancer (FIRE-9 - PORT / AIO-KRK-0418)","route":"/trials/nct05008809/"},{"id":"nct06899477","kind":"trial","name":"Pre-Operative Treatment in REseCTable COlon CanceR","route":"/trials/nct06899477/"},{"id":"nct03671252","kind":"trial","name":"Prospectively Randomized Control Clinical Trial of FOLFOXIRI Preoperative Chemotherapy Alone on Rectal Cancer in Local Advance Comparing to Oral Capecitabine Co","route":"/trials/nct03671252/"},{"id":"tribe","kind":"trial","name":"TRIBE","route":"/trials/tribe/"},{"id":"tribe2","kind":"trial","name":"TRIBE2","route":"/trials/tribe2/"}]}}