Accumulating evidence suggests that post-diagnostic insulin levels may influence colorectal cancer (CRC) survival. Yet, no previous study has examined CRC survival in relation to a post-diagnostic diet rich in foods that increase post-prandial insulin levels. We hypothesized that glycemic and insulin scores (index or load; derived from food frequency questionnaire data) may be associated with survival from specific CRC subtypes sensitive to the insulin signaling pathway. We prospectively followed 1,160 CRC patients from the Nurses' Health Study (1980-2012) and Health Professionals Follow-Up Study (1986-2012), resulting in 266 CRC deaths in 10,235 person-years. CRC subtypes were defined by seven tumor biomarkers (KRAS, BRAF, PIK3CA mutations, and IRS1, IRS2, FASN and CTNNB1 expression) implicated in the insulin signaling pathway. For overall CRC and each subtype, hazard ratio (HR) and 95% confidence interval (95% CI) for an increase of one standard deviation in each of glycemic and insulin scores were estimated using time-dependent Cox proportional hazards model. We found that insulin scores, but not glycemic scores, were positively associated with CRC mortality (HR=1.19, 95% CI=1.02-1.38 for index; HR=1.23, 95% CI=1.04-1.47 for load). The significant positive associations appeared more pronounced among PIK3CA wild-type cases and FASN-negative cases, with HR ranging from 1.36 to 1.60 across insulin scores. However, we did not observe statistically significant interactions of insulin scores with PIK3CA, FASN, or any other tumor marker (p interaction>0.12). While additional studies are needed for definitive evidence, a high-insulinogenic diet after CRC diagnosis may contribute to worse CRC survival. What's new? Elevated circulating insulin levels are associated with colorectal cancer (CRC) pathogenesis and may also be linked to CRC survival. According to this report, insulin's contribution to CRC prognosis are potentially reflected in differences in the insulinogenic diet-mortality association by tumor biomarkers related to the insulin signaling pathway. In a prospective cohort study of CRC patients, a high-insulinogenic diet was linked to poor CRC survival primarily when CRCs were of PIK3CA wild-type or FASN-negative, though the interactions were not statistically significant. Insulin scores were also significantly associated with all-cause mortality among FASN-negative cases. No associations were detected between glycemic scores and CRC mortality.