Compare overall survival (OS) between microsatellite instability (MSI) high and MSI-stable and analyze the effect of chemotherapy on OS. National cancer database was queried for patients diagnosed with colorectal adenocarcinoma between 2010 and 2016. We evaluated the OS and the chemotherapy effect using Kaplan–Meier estimates and multivariate Cox regression analyses. Total of 30,436 stage II patients and 30,302 stage III patients were included. In stage II with high-risk features and MSI-high, patients who received chemotherapy had better OS compared to patients who didn't receive chemotherapy. The same was found in stage II with no high-risk features and MSI-high group. Stage II colorectal cancer patients with high-risk features and MSI-high who received chemotherapy have better OS compared to patients who didn't receive chemotherapy.