Background: Downsizing with chemotherapy (CT) unresectable liver-limited disease (LLD) can permit resection and prolonged survival in patients (pts) with colorectal cancer (CRC). We assessed the value of adding panitumumab (P) to standard CT in this setting. Methods: This was a phase II, open-label, randomized, multicenter study which included pts≥18 years with wild-type (WT) KRAS exon 2 metastatic CRC and LLD fulfilling one of the following criteria: ≥4 metastases; at least 1 metastasis>10 cm in diameter; or technically not resectable. Pts were randomized 1:1 to receive P-FOLFOX4 or P-FOLFIRI every two weeks. The primary endpoint was the objective response rate. Results: There were77 pts analyzed (38 received P-FOLFOX4 and 39 P-FOLFIRI). Not confirmed response was noted in 70.1% pts (73.7% with P-FOLFOX4 and 66.7% with P-FOLFIRI). After a median of 8 P infusions in both groups, 51.9% underwent surgical resection of liver metastases (44.7% and 59.0%, respectively). The resection rate (R0+R1) was 77.5% (76.5% and 78.3%). Median progression-free survival was 12.5 months with P-FOLFOX4 and 12.6 months with P-FOLFIRI (p=0.943). Preliminary median overall survival was 32.5 and 42.4 months. Median pre-surgery relative dose-intensity (RDI) for panitumumab was 79.8% with P-FOLFOX4 and 87.5% with P-FOLFIRI, and RDI for CT was 83.0% and 88.7%. Peri-operative safety was similar between groups (22.2% and 18.5% of pts with any adverse event). Neutropenia grade 3/4 (P-FOLFOX4 39.5% vs P-FOLFIRI 10.3%; p=0.0029) and neuropathy (P-FOLFOX4 13.2% vs P-FOLFIRI 0%;p=0.025), were the only statistically significant differences in grade 3/4 adverse events. It was possible to determine the RAS status (exon 2,3,4 of KRAS/NRAS) in 83.1% of the pts. In the subset of pts with RAS WT the response rate increases to 75.5% pts (77.8% with P-FOLFOX4 and 73.1% with P-FOLFIRI). Conclusions: In this selected population with WT KRAS CRC and LLD, panitumumab plus CT offers the possibility of rapid tumour shrinkage and potentially curative hepatic resection. Similar efficacy and safety results were obtained with either P-FOLFOX4 or P-FOLFIRI schema. Clinical trial information: NCT00885885.