Aim: The key purposes of the treatment of metastatic malignancies are to extend survival and maintain the quality of life. Recently it has been emphasized in the scientific literature that the maintenance of maximal dose intensity is not always beneficial. Method: We examined the effectiveness of first-line mFOLFIRI-based treatments used in mCRC indication in 515 patients, treated between 1 January 2013 and 31 December 2018 at the Department of Oncotherapy of the University of Pécs, on a basis of real-world retrospective data analysis. We studied the effect of decreased dose intensity treatment modifications on patient survival. Results: 45% of all patients achieved the optimal relative dose intensity (RDI) of 85%, and the median progression-free and overall survival (mPFS, mOS) were 199 and 578 days, compared to 322 and 743 days, (mPFS p < 0.0002, 1 y (year) PFS OR (odds ratio) 0.39 (95% CI: 0.26–0.56) and mOS p = 0.0781, 2 yrs OS OR 0.58 (95% CI: 0.39–0.85), respectively) in the group of patients not achieving the RDI of 85%. Conclusions: Decreased dose intensity did not reduce the effectiveness of treatment; in fact, there was a significant improvement in most of the analyzed parameters. The option of reduced dose intensity, which shows the same or even better results with less toxicity, should definitely be considered in the future palliative treatment of mCRC patients.