Drugs included:
- FOL = Leucovorin (folinic acid)
- F = 5-Fluorouracil (5-FU)
- OX = Oxaliplatin
- IRI = Irinotecan
So, it’s essentially FOLFOX (5-FU, leucovorin, oxaliplatin) + Irinotecan.
Clinical Uses
- Metastatic colorectal cancer (mCRC):
- Especially in patients with good performance status (ECOG 0–1) who can tolerate intensive chemotherapy.
- Often used in fit, younger patients to maximize response and potentially allow conversion to resection (e.g., liver metastasectomy).
- Sometimes combined with biologics like bevacizumab.
Dosing Example (biweekly, Day 1 = start of cycle)
- Oxaliplatin: 85 mg/m² IV day 1
- Irinotecan: 165 mg/m² IV day 1
- Leucovorin: 200 mg/m² IV day 1 (given with oxaliplatin + irinotecan)
- 5-FU: 3200 mg/m² continuous infusion over 48 hours (no bolus in some regimens to reduce toxicity)
- Cycle: every 2 weeks
(Dose modifications are common based on toxicity, especially GI and hematologic)
Toxicities
- Myelosuppression (neutropenia, anemia, thrombocytopenia)
- GI: severe diarrhea (irinotecan), mucositis, nausea/vomiting
- Neurotoxicity: peripheral neuropathy (oxaliplatin, cumulative)
- Hand-foot syndrome (5-FU, especially if bolus is included)
- Fatigue, alopecia
- Risk of febrile neutropenia higher than with doublets (FOLFOX or FOLFIRI).
Clinical Pearls for Oncology Pharmacist
- Reserved for fit patients due to high toxicity.
- Dose intensity must be balanced against quality of life.
- If not tolerated, de-escalate to FOLFOX or FOLFIRI.
- Monitor CBC, renal, liver function, and assess for neuropathy before each cycle.
Summary:
FOLFOXIRI = 5-FU + leucovorin + oxaliplatin + irinotecan.
Used mainly in metastatic colorectal cancer to improve response rates, especially in younger/fit patients, but associated with high toxicity compared to doublet regimens.

