Purpose To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780). Methods Patients with previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour RAS status was a prespecified objective. Exploratory analyses included early tumour shrinkage (ETS) and depth of response (DpR). Results One hundred seventy patients had RAS WT and 156 had RAS WT/ BRAF WT mCRC. Median PFS was longer for panitumumab versus bevacizumab in the RAS WT (12.8 vs 10.1 months; hazard ratio (HR) = 0.68 95% confidence intervals (CI) = 0.48–0.96; p =  0.029) and RAS WT/ BRAF WT (13.1 vs 10.1 months; HR = 0.61 95% CI = 0.42–0.88; p =  0.0075) populations. Median OS (68% OS events) for panitumumab versus bevacizumab was 36.9 versus 28.9 months (HR = 0.76 95% CI = 0.53–1.11; p =  0.15) and 41.3 versus 28.9 months (HR = 0.70 95% CI = 0.48–1.04; p =  0.08), in the RAS WT and RAS WT/ BRAF WT populations, respectively. Median DoR (11.4 vs 9.0 months; HR = 0.59 95% CI = 0.39–0.88; p =  0.011) and DpR (65.0 vs 46.3%; p =  0.0018) were improved in the panitumumab group. More panitumumab patients experienced ≥30% ETS at week 8 (64 vs 45%; p =  0.052); ETS was associated with improved PFS/OS. No new safety signals occurred. Conclusions First-line panitumumab + mFOLFOX6 increases PFS versus bevacizumab + mFOLFOX6 in patients with RAS WT mCRC.