Background: It remains unresolved which antibody, anti-vascular endothelial growth factor or anti-epidermal growth factor receptor antibody, is the best targeted agent to combine with chemotherapy for patients having liver-limited metastases of KRAS Exon 2 or RAS wild-type colorectal cancer. Methods: The ATOM trial is a Japanese multicenter, randomized phase II study comparing modified FOLFOX6 plus bevacizumab with modified FOLFOX6 plus cetuximab in patients with unsuitable liver metastases for resection (5 or more liver metastatic lesions and/or maximum tumor diameter > 5cm). Patients are enrolled and randomly assigned to receive either treatment in 1:1 ratio from May 2013 to April 2016. Stratification factors for randomization are synchronous or metachronous liver metastases, number (1–4 or ≥ 5) and size ( ≤ 5 cm or > 5 cm) of metastatic lesions, and adjuvant chemotherapy with or without oxaliplatin-containing regimen. All patients are to be followed up to March 2017. Primary endpoint is progression-free survival (PFS). We employed a selection design based on hazard ratios. Planned sample size is 120 patients with 84 estimated PFS events based on the hypothesis to select the superior treatment with the 75.0 % selection probability if the difference of both treatments is a 1-year PFS rate of 5% and the inferior treatment has a 1-year PFS rate of 50%. Secondary endpoints are response rate, tumor shrinkage at week 8, liver resection rate, time to treatment failure, overall survival, quality of life, and adverse events. Exploratory endpoints include pathologic and morphologic assessments, which will be investigated in collaboration with radiologists and pathologists. The plasma factors relating to tumor angiogenesis are assessed sequentially to explore the association with treatment efficacies. As of Aug 20^th 2015, 102 patients were enrolled. The results from this trial will show which targeted agents should be used to treat liver-limited diseases from colorectal cancer with WT RAS tumor. Clinical trial information: NCT01836653