When fire incidents occur in concrete frame buildings, a locally-heated column will be simultaneously subjected to non-standard fire attack, restraint, eccentric loads and concrete spalling. Coupled with the deteriorations of material strength and stiffness at elevated temperatures, concrete spalling may cause premature failure of the column. In this paper, the practical range of restraint due to the heated column’s different thermal response against its adjacent framing structural elements, is studied numerically to compare with the result of a previously-published analytical approach. Then, experimental observations on concrete spalling of twelve full-scale reinforced concrete column specimens in three series cast from different concrete compressive strengths and subjected to simultaneous actions of uniaxial/biaxial bending, axial restraint, and non-standard fire exposure are presented. It was shown that the concrete spalling occurred earlier and more severely on the columns cast from higher concrete strength. Besides, biaxially-loaded columns were more susceptible to concrete spalling than those under uniaxial bending. Furthermore, the fire durations of the tested columns predicted by the finite-element model ignoring concrete spalling were all longer than those recorded experimentally. Finally, the authors introduce a Gaussian Process regression model that is capable of predicting the similar trends observed from both numerical and experimental studies.