A 58-year-old woman was confirmed as having multiple liver metastases after undergoing a high anterior resection for a sigmoid colon tumor. She was administered bevacizumab+FOLFOX as the first regimen and bevacizumab+FOLFIRI and S-1 and irinotecan (IRIS)therapy as the second regimen. During this treatment she also underwent hepatectomy 3 times and radiofrequency ablation once. She was administered panitumumab+irinotecan as the third regimen and, due to the presence of multiple pulmonary metastases, was subsequently considered to have had a partial response (PR). Because she subsequently developed progressive disease (PD), she received the fourth regimen as part of a clinical trial (TAS102) in another hospital. Cetuximab+irinotecan was administered as the fifth regimen after PD and the tumor was found to have reduced in size by 23%upon computed tomography (CT) 2 months later. Although stable disease (SD) was achieved, she was subsequently administered regorafenib for 8 months as a sixth regimen after the disease progressed a second time. In some cases of KRAS wild type metastatic colorectal cancer, re-challenging with an anti-epidermal growth factor receptor (EGFR) monoclonal antibody seems to be an effective strategy for reducing tumor mass.