e14080 Background: At present, systemic chemotherapy is the only established treatment in patients with unresectable colorectal liver metastases (CRLM). The regimen combining irinotecan or oxaliplatin to 5-FU/LV is recommended as a first and second line treatment. However, after failure of oxaliplatin- or irinotecan-based combination chemotherapy, there is no effective regimenremained. This pilot clinical trial explored the feasibility, safety, and efficacy of sequential chemotherapy of hepatic arterial infusion of FOLFOX and FOLFIRI with Intravenous Bevacizumab in unresectable CRLM after systemic chemotherapy failure. Methods: Patients with unresectable CRLM and history of systemic chemotherapy failure were treated with HAI oxaliplatin (35 mg/m2 2 hours: HAI-FOLFOX) or irinotecan (50 mg/m2 2 hours: HAI-FOLFIRI) followed by 5FU (1500mg 46hours) combined with intravenous Bevacizumab (200mg 90min) and LV (200mg 2hours) every 2 weeks until disease progression. Basically, HAI-FOLFOX was applied first, and after disease progression or limiting toxicity, HAI-FOLFIRI followed when the patient was still able to receive treatment. Results: Fourteen consecutive patients (median age 65 years; mean therapeutic term of prior systemic chemotherapy regimens,533 ± 266 days) were included, of whom 11 (79%) had previously received oxaliplatin (n =5), irinotecan (n = 2), or both (n = 4). Patients received a median of 13 cycles of HAI-FOLFOX (range 4–32) and among those, 7 patients sequentially received a median of 22 cycles of HAI-FOLFIRI (range 2–42). There was no technical nonfeasibility to discontinue treatment. The regimen was generally well tolerated; the most common side effects were grade 1 fatigue, anorexia, and/or hypertension. The complete and partial response rate totaled 71.4% in this sequential therapy. Median survival time was 20.1 months. Conclusions: A sequential chemotherapy of hepatic arterial infusion of FOLFOX and FOLFIRI with intravenous bevacizumab is feasible, safe, and shows promising activity in unresectable CRLM after systemic chemotherapy failure.