The influence of nanoscale confinement on the thermally induced ring-opening polymerization (ROP) of three different monofunctional benzoxazines (Bzs) was highlighted for the first time. The Bzs were solution-loaded or blended in/with a titanium-based metal-organic framework (MOF), i.e., MIL-125-based. The successful infiltration of the Bzs within the MOF was confirmed through comprehensive analyses using FTIR, BET, and DSC techniques. Remarkably, the nanoconfinement exhibited exceptional promotion of the Bzs ROP, resulting in a significant decrease in the onset temperature of the corresponding exotherms of as much as 127 °C for the nonsubstituted monomer. GPC traces revealed that high-molecular-weight polybenzoxazines (PBzs) were formed when fluorine-substituted Bz polymerized in the MOF-confined nanospaces. The catalytic role of nanoconfinement was further supported by analyzing the effective activation energy through the isoconversional method of Starink. ROP of the Bz-MIL-125 blend, where the effect of nanoconfinement was absent, demonstrated the catalytic role of MIL-125 with a less pronounced impact compared to the nanoconfined system.