Background: The treatment of locally advanced colon cancer faces many challenges and new approaches are needed. Neoadjuvant chemotherapy has proven valuable in several tumors, but it has not been elucidated in colon cancer. One major reason has been the lack of validated methods for selection, but recent improvement in CT scanning has allowed for identification of high-risk patients in need of adjuvant chemotherapy. Methods: Patients with resectable colon cancer fulfilling the following criteria were offered inclusion; Histopathological verification of adenocarcinoma, T3 tumor on CT scan with extramural tumor invasion > 5 mm or T4 tumor, age ≥ 18 years, PS ≤ 2, adequate hematology, and informed consent. Patients with KRAS, BRAF, or PIK3CA mutation or unknown mutational status received 3 cycles of capecitabine 2000 mg/m²days 1-14 q3w and oxaliplatin 130 mg iv day 1 q3w. Wildtype patients received the same chemotherapy supplemented with panitumumab 9 mg/kg iv q3w. After the operation, patients fulfilling the international criteria for adjuvant chemotherapy received 5 cycles of the same chemotherapy without panitumumab. Patients not fulfilling the criteria (converted patients) were offered follow-up only. The primary endpoint was the fraction of converted patients. Secondary endpoints were 2-year disease free survival (DFS) and toxicity. The study was approved by the Regional Scientific Ethical Committee (S-20100014) and registered at ClinicalTrials.gov (NCT01918527). Results: The study included 77 patients. The conversion rate was 42% in the wildtype group compared to 51% in patients with a mutation. The objective response rate by CT scan was 45%. Three patients had complete pathological remission. The cumulative recurrence rate in converted vs. non-converted patients was 3% vs. 27% (p=0.003) translating into a 2-year DFS of 96% vs. 54% (p=0.004). Toxicity was manageable and 90% received ≥ two cycles of the three planned cycles of neoadjuvant chemotherapy. Conclusions: Neoadjuvant chemotherapy in colon cancer is feasible and the results suggest that a major part of the patients can be spared adjuvant chemotherapy. A randomized trial is warranted. Clinical trial information: NCT01918527.