Background. Treatment of patients with metastatic colorectal cancer (MCRC) previously exposed to oxaliplatin-based regimen is challenging. Efficacy and toxicity of bevacizumab plus irinotecan-based regimens were assessed in the second-line treatment of MCRC patients. Patients and Methods: Forty patients with a median age of 53 years (range, 31-75) were retrospectively evaluated. Patients progressing or relapsing after treatment with oxaliplatin-based regimens were given bevacizumab 5 mg/kg every 2 weeks in combination with irinotecan-based regimens. All patients had previously received oxaliplatin either in the adjuvant setting (n = 8) or for metastatic disease (n = 32). Results: Three patients achieved a complete response (7.5%),5 partial responses (12.5%) and 14 (35%) stable disease resulting in an overall response rate of 20%. Median progression-free survival was 6 months (95% CI, 4.0-8.0) with a median overall survival of 14 months (95% CI, 10.2-17.8). One-year survival rate was 55.9%. Grade 3-4 toxicities were as follows: neutropenia (n = 15, 37.5%), febrile neutropenia (n = 2, 5%), diarrhea (n = 11, 27.5%), nausea and vomiting (n = 3, 7.5%), gastrointestinal perforation (n = 2, 5%), and thromboembolism (n = 2, 5%). Conclusion: Bevacizumab plus irinotecan-based combination chemotherapy is an active and safe treatment option in patients failing oxaliplatin-based therapy.