Background: The ASPECCT study showed panitumumab (Pmab) is non-inferior to cetuximab (Cmab) for chemotherapy-refractory and intolerant wild-type (WT) KRAS exon2 metastatic colorectal cancer (mCRC). In the subgroup analysis, Pmab provided more favorable outcomes than Cmab for patients (pts) previously treated with bevacizumab (Bmab). However, some reports suggested that anti-EGFR antibody (anti-EGFR) efficacy was reduced when received within 6 months of last administration of Bmab. In this study, we aim to evaluate the difference in efficacy between Pmab and Cmab in pts who received prior Bmab and were treated with anti-EGFR after a short interval. Methods: We retrospectively evaluated pts treated with anti-EGFR and irinotecan (IRI) after failure of Bmab, fluoropyrimidine, oxaliplatin, and IRI at two institutions. The main inclusion criteria were WT KRAS exon2 mCRC, ECOG PS 0-2, and no prior administration of anti-EGFR within 6 months after Bmab. Results: From Sep. 2008 to Mar. 2016, 124 consecutive pts met the inclusion criteria (Pmab/Cmab, 30/94). Pts’ characteristics were as follows (Pmab/Cmab): median age (range): 63/62 (38-76/27-82); male, 63%/72%; ECOG PS 0, 43%/27%; PS1, 57%/66%; PS2 0%/7%; tumor in left colon, 87%/76%; histology (por, muc), 10%/16%; ≥2 metastases, 67%/66%; ≥1 subsequent therapy, 73%/63%. Overall response and disease control rates in Pmab/Cmab were 31%/26% and 69%/67%, respectively. In Pmab/Cmab, the median overall survival was 15.8/12.2 months (HR, 0.62; 95% CI, 0.4-0.97; P=0.04) and the median progression-free survival was 6.5/5.5 months (HR, 0.75; 95% CI, 0.49-1.16, P=0.20). The adjusted HR with 10 covariates such as age, gender, PS, tumor location, histology, primary tumor resection, number of metastatic sites, liver limited disease, time from diagnosis of metastasis and initiation date of anti-EGFR plus IRI was 0.61 for PFS (p=0.1) and 0.61 for OS (p=0.04). Conclusions: Pmab plus irinotecan showed favorable outcomes compared with Cmab plus irinotecan in pts with WT KRAS exon2 mCRC within 6 months between the last administration of Bmab and initial anti-EGFR.