Weekly cetuximab plus irinotecan-based regiments are standard first- and second-line chemotherapy for patients with KRAS wild-type metastatic colorectal cancer (mCRC). However, the chemotherapy regimens are given every 2 weeks, which is asynchronous with cetuximab weekly administration. This study investigated the efficacy and safety of biweekly cetuximab administration in patients with mCRC. Twenty-six patients with KRAS wild-type mCRC, who received biweekly cetuximab plus FOLFIRI/irinotecan as first/second-line chemotherapy, at least three cycles of cetuximab and once CT evaluation in West China Hospital from May 2010 to February 2013, were retrospectively analyzed. The median number of cetuximab administrations was 8.3 (range 3-20). Fourteen patients received FOLFIRI as first-line therapy; response rate was 50.0%; median PFS was 8.8 months (95% CI 4.9-12.7). Ten patients received FOLFIRI and two patients received irinotecan as second-line therapy; response rate was 33.3%; median PFS was 4.6 months (95% CI 0.9-8.3). The toxicity was similar to weekly cetuximab combination schedules. Rash was observed in 69.2% of evaluable patients (grade 3 in 7.7%). Overall, our results show that biweekly cetuximab plus FOLFIRI/irinotecan may be as effective and safe as the standard weekly schedule.