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Purpose: A phase I study of FOLFIRINOX3-bevacizumab (bFOLFIRINOX3)defined the RP2D for irinotecan at 70 mg/m² and showed promising activity. This phase II trial aimed to evaluate the efficacy of bFOLFIRINOX-3 in chemorefractory metastatic colorectal cancer (mCRC)., Methods: In phase II, chemorefractory mCRC were enrolled. The regimen tested consisted of bevacizumab (5 mg/kg), folinic acid(400 mg/m²), 5-fluorouracil (2400 mg/m² for 46 h), oxaliplatin (85 mg/m²) and irinotecan (70 mg/m² administered before and after infusion of 5-fluorouracil). The primary endpoint was efficacy defined by 2-month progression-free survival(PFS). Secondary endpoints included objective response, median PFS, overall survival (OS) and toxicity., Results: 32 patients were enrolled (October 2018 to December 2022); median age 62.5 years (range 32-78). The majority had been treated with several previous lines of chemotherapy (median 3, range [1-8]). Median follow up was 12 months (range [1.5-12]). Two-month PFS was 96.9%. Best objective response rate (ORR) was 28.1%. Median PFS was 9.4 months (95%CI [6.9;11.5]) and median OS was not reached (95% [11.6; NR]). Grade 3 adverse events occurred in 81.2%; mostly diarrhea (37.5%) and neutropenia (12.5%). Grade 3 diarrhea consistently resolved after irinotecan dose reduction. The most common drug-related adverse events (all grades) were diarrhea (96.9%), fatigue (68.8%), nausea (68.7%), anemia (56.3%), peripheral neuropathy (53.4%) and thrombopenia (40.6%)., Conclusion: The combination of bFOLFIRINOX-3 yielded 2-month PFS of 96.9% and best ORR of 28.1%, and was well tolerated. These results are promising in chemotherapy refractory mCRC and provide a rationale for future randomized phase III trials., Clinical Trial Registration: NCT03795311 (clinicaltrials.gov).