Objectives: A growing number of older patients with cancer require well-founded clinical decision-making. Frailty screening is suggested as a service to improve outcomes in vulnerable older patients with cancer. This prospective study examined the value of frailty screening to predict rapid functional decline, rapid progressive disease (PD) and shorter overall survival (OS) in older patients with gastrointestinal cancer receiving palliative chemotherapy. Materials and Methods: Patients aged ≥70 years were screened for frailty in an oncologic department after clinical decision but before starting palliative chemotherapy. Screening was repeated at first response evaluation after approximately two months of chemotherapy. Frailty screening tools included performance status (PS), Charlson Comorbidity Index, G-8 using two different cut-offs (G814,G811), VES–13, Timed-Up-and-Go, Handgrip strength and falls. Results: A total of 170 patients were included, median age was 75.5 (70–88) years and 65.9% were male. The frequency of frailty varied from 14% to 74% according to the chosen frailty tool. In multivariate analysis G814 predicted OS (HR 1.5; 95%CI 1.0–2.4), whereas G811 predicted PD (OR 2.4; 1.1–5.6) and OS (HR 2.1; 1.4–2.9). VES-13 predicted functional decline (OR 3.5; 1.0–11.6), PD (OR 3.5; 1.5–8.4) and OS (HR 1.7; 1.2–2.4). Timed-Up-and-Go predicted OS (HR 1.8; 1.1–2.7). Handgrip strength and falls predicted functional decline (OR 4.5; 1.1–19 and OR 6.1; 1.4–25.8, respectively). PS predicted PD (OR 6.2; 2.6–14.7) and OS (HR 2.2; 1.5–3.2). Conclusion: VES-13 was useful for predicting all three endpoints of interest. Frailty tools covering domains of functioning and nutrition are suggested for older patients with advanced gastrointestinal cancer.