Background: The optimal sequence of chemotherapeutic agents is not firmly established for the treatment of metastatic colorectal cancer (mCRC). This phase II multi-centre study investigated the efficacy and tolerability of a standard capecitabine plus irinotecan (XELIRI) regimen with bevacizumab in previously untreated patients with mCRC. Methods: Patients received intravenous irinotecan 175 mg/m2 on day 1 and oral capecitabine 1000 mg/m2 (800 mg/m2 for patients >65 years of age) twice daily on days 2–8, followed by a 1-week rest, and bevacizumab 5 mg/kg as an intravenous infusion on day 1 every 2 weeks. Results: Seventy-seven patients were included in the intention-to-treat and safety populations. Progression-free survival at 9 months was 61%. The overall response and disease control rates were 51% and 84%, respectively. Median progression-free and overall survival times were 11.9 and 24.8 months, respectively. 48 patients (62%) had at least one grade 3/4 adverse event, the most common being asthenia, diarrhoea and neutropenia. Quality of life varied little over the study period with mean visual analogue scale general health scores ranging from 71 to 76 over cycles 1–11. Conclusion: Our study found irinotecan and capecitabine administered fortnightly with bevacizumab in patients with mCRC to be an effective and tolerable regimen. Trial registration: clinicaltrials.gov identifier NCT00875771. Trial registration date: 04/02/2009. Keywords: Irinotecan, Capecitabine, Bevacizumab, Metastatic colorectal cancer, Chemotherapy