Background: ICI is reserved for mismatch repair (MMR) deficient and high tumor mutation burden (TMB) CRC patients in the current clinical practice. Identifying clinicopathological factors predicting response to ICI beyond MMR status could help effectively utilize ICI in this population. This is a retrospective review of advanced CRC (recurrent or metastatic) patients treated with ICI at an academic institute to identify the risk factors (RF) for poor outcomes. Methods: CRC patients who received at least one dose of ICI for between 1/1/2015 and 7/31/2021 at the Ohio State University were included in the study. The patient's baseline (BL) characteristics (at the first dose of ICI) were extracted with immune-related adverse events (irAE) details and survival outcomes. Descriptive statistics were used, Fisher exact test to compare categorical variables, log-rank test rank test for survival outcomes, and logistic regression model for categorical outcomes using JMP Pro 16 (SAS Institute Inc., Cary, NC). Results: Our cohort has 46 advanced patients (37 colon and 7 rectal), the median age was 51 years (range 26-82) with 52% females, 95% Caucasians, 76% had metastatic disease (47% and 32% had liver and lung metastases or mets, respectively), 41% were mismatch repair (MMR) deficient, and 30% had KRAS exon two mutations. About 30% and 43% got ICI in the first line and ≥ 4 lines, respectively. Most patients received pembrolizumab (57%), followed by nivolumab (28%), atezolizumab (11%), and durvalumab (4%). Chemotherapy and ICI combination was given in 39%. irAEs were reported in 19% (n = 9). Median overall survival (OS) and progression-free survival (PFS) were 37 months (m) (95% confidence interval [CI], 14-NR) and 15m (95% CI, 7-35), respectively. Baseline (before the first ICI dose) albumin (p = 0.005), hemoglobin or Hb (p = 0.001), and the red cell count or RBC (p = 0.003) were negatively related to OS, while platelet to lymphocyte ratio or PLR (p = 0.01) and alkaline phosphatase levels (p = 0.03) were positively related to OS. High BL white cell count (WBC) (p = 0.04), alkaline phosphatase or ALP (p = 0.01), and low albumin (p = 0.002) and alanine transferase or ALT (p = 0.005) significantly impacted the OS. Other significant predictors are discussed in the table below. Conclusions: Our study provides insights into baseline tumor characteristics (such as lung/liver mets, KRAS exon 2 mutations, and MMR status) and lab values (such as RBC, Hb, PLR, albumin, ALP, and ALT) that could predict tumor response in CRC patients treated with ICI. These associations must be validated in larger studies.