Background: About 50% of diagnoses of colorectal cancer (CRC) occur in patients (pts) older than 70 years. Though a comprehensive geriatric assessment (CGA) is recommended for proper management of older cancer pts, there is still no consensus on the best form of geriatric assessment. We investigated possible prognostic factors in elderly metastatic (m)CRC pts in a real-world setting, focusing on the role of the oncological-multidimensional prognostic index (onco-MPI). Methods: Pts aged ≥ 70 years with mCRC referred to the Medical Oncology 1 Unit from May 2010 to May 2017 were assessed by a multidisciplinary team and received a basal CGA. Onco-MPI was calculated by a validated algorithm as a weighted linear combination of the CGA domains, as previously described. The following 3 different prognostic groups were identified: low (scores 0.0-0.46), medium (scores 0.47-0.63) and high risk (scores 0.64-1.0). Results: A total of 206 mCRC pts were included, 123 males. Mean age was 76.1 years (69.2-90.8). ECOG PS was < 2 in 90% and mini-mental state examination was ≥ 24 in 85% of pts. Primary tumor was located in rectum, left and right side in 18%, 42% and 40% of pts, respectively. RAS and BRAF mutations were detected in 44% and 9% of pts, respectively. According to onco-MPI score, 32%, 39% and 28% of cases were low, medium and high risk, respectively. According to CGA as per Balducci’s criteria, 56% of pts were classified as fit, 31% vulnerable and 13% frail. Median overall survival (OS) was 26 months (95% CI 19.7-32.4). The following factors were significantly associated with OS: ECOG PS (0-1 vs > 1, 31% vs 15%, p = 0.004); onco-MPI score (low vs medium vs high risk, 29% vs 38% vs 19%, p = 0.005), treatment (monotherapy vs doublet vs triplet, 20% vs 31% vs 30%, p = 0.01). No significant difference in OS was observed in CGA-based groups (p = 0.15). In high onco-MPI score, doublet-regimen correlated with higher OS compared to monotherapy (79% vs 51%, p = 0,03). Conclusions: Onco-MPI emerged as a significant prognosticator in mCRC elderly pts. It may be useful in daily clinical practice for driving decision-making in this age group. Thanks to its marked standardization it may be also applied in clinical trials.