The incidence of colorectal cancer is higher in men than in women, amounting to 15% of cancer-related diseases as a whole. As such, undesirable effects, arising from the administration of current chemotherapeutic agents (the FOLFIRI/FOLFOX combinations), which are exerted on the remaining non-cancerous tissues and/or cells, have contributed to the occurrence of resistance to multiple drugs, thus markedly reducing their efficacy. However, the delivery of chemotherapeutic agents may be improved and their action may be more selectively targeted to diseased tissues/cells by means of developing biotechnologies and nano‑techniques. Thus, the current focus is on creating biological tissue and related tumor models, by means of three‑dimensional (3D) spheres, in an attempt to bridge the gap between results obtained in the pre‑clinical phase and promising outcomes obtained in clinical trials. For this purpose, the characterization and use of so‑called 'multicellular tumor spheroids', may prove to be invaluable. In this study, we focus on describing the efficacy of a model 3D system as compared to the traditional 2D tumor spheres in determining drug response, highlighting a potentially greater effect of the drugs following the encapsulation of respective liposomes. The results obtained demonstrate the successful preparation of a suspension of liposomes loaded with folinic acid, oxaliplatin and 5‑fluorouracil (5‑FU), and loaded with meso‑tetra (4‑sulfonatophenyl) porphyrin. Following its use on HT‑29 colorectal cancer cells, an important comparative reduction was noted in the viability of the HT‑29 cells, demonstrating the efficacy of multicellular tumor spheroids carrying liposomes loaded with therapeutic drugs. These findings indicate that the method of drug encapsulation in liposomes may improve the treatment efficacy of chemotherapeutic agents.