Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown clinical activity in metastatic colorectal cancer patients when used as either a first-line or second-line treatment. Here, we evaluated the efficacy and safety of bevacizumab plus FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) or FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin) in metastatic colorectal cancer cases after failure to FOLFIRI and FOLFOX. Between October 2004 and February 2007, the data on 42 patients with metastatic colorectal cancer after failure of FOLFIRI and FOLFOX were reviewed retrospectively. All patients were treated with bevacizumab plus FOLFIRI or FOLFOX. The median patient age was 57.0 years. The ECOG performance status was 0 or 1 in 27 patients (64.3%). The number of previous chemotherapy regimens was >/=3 in 35 patients (83.3%). Thirty-nine patients were evaluable for response. Four patients had partial responses (PRs) and no patient had a complete response (CR), giving an overall response rate of 9.5%. Twenty-two patients (52.4%) had stable disease and 13 patients (31.0%) showed progressive disease. With a median follow-up time of 12.9 months (range 1.0-30.0 months), the median progression-free survival time and the median overall survival time were 5.3 and 9.5 months, respectively. Grade 3 or 4 neutropenia developed in 18 patients (42.9%), including febrile neutropenia in 4 patients (9.5%). Common non-hematologic toxicities were fatigue (21.4%), neuropathy (21.4%), and mucositis (21.4%). Grade 2 or 3 hypertension occurred in 4 patients (9.6%), and grade 1 or 2 proteinuria was seen in 16 patients (38.1%). The frequencies of adverse events related BV, such as bleeding, thrombosis, and gastrointestinal perforation, were within the ranges of previous reports. However, there were no treatment-related deaths. The combination of bevacizumab plus FOLFIRI or FOLFOX showed modest activity and was relatively tolerable in patients with metastatic colorectal cancer refractory to both FOLFIRI and FOLFOX.