Abstract Background AJCC staging and other prognostic tools fail to account for stage-independent variability in outcome. We developed a prognostic classifier adding Immunoscore to clinicopathological and molecular features in patients with stage III colon cancer. Methods Patient (N = 559) data from the FOLFOX arm of adjuvant trial NCCTG N0147 were used to construct Cox models for predicting disease-free survival (DFS). Variables included age, gender, T stage, positive lymph nodes (+LNs), N stage, performance status, histologic grade, sidedness, KRAS/BRAF, mismatch repair, Immunoscore (CD3 +, CD8 + T-cell densities). After determining optimal functional form (continuous or categorical ) and within Cox models, backward selection was performed to analyze all variables as candidate predictors. All statistical tests were two-sided. Results Poorer DFS was found for tumors that were T4 vs T3 [HR 1.76, 95% CI 1.19, 2.60, p = 0.004], right vs left sided [HR 1.52, 95% CI 1.14, 2.04, p = 0.005], BRAF V600E[HR 1.74, 95% CI 1.26, 2.40, p < 0.001], mutant KRAS [HR 1.66, 95% CI 1.08, 2.55, p = 0.02], and low vs high Immunoscore [HR 1.69, 95% CI 1.22 to 2.33, p = 0.001] (all p ≤ 0.02). Increasing number of +LNs and lower continuous Immunoscore were associated with poorer DFS that achieved significance (both p <0.0001). After number of +LNs, T stage and BRAF/KRAS, Immunoscore was the most informative predictor of DFS shown multivariately. Among T 1-3 N 1 tumors, Immunoscore was the only variable associated with DFS that achieved statistical significance. A nomogram was generated to determine the likelihood of being recurrence-free at 3 years. Conclusions The immunoscore can enhance the accuracy of survival prediction among patients wthe stage III colon cancer.