In the present paper, we face the problem of classifying classes of orientable PL $5$-manifolds $M^5$ with $h \geq 1$ boundary components, by making use of a combinatorial invariant called {\it regular genus} ${\cal G}(M^5)$. In particular, a complete classification up to regular genus five is obtained: $${\cal G}(M^5) = \gG \leq 5 \Longrightarrow M^5 \cong \#_{\varrho - \gbG}(\bdo) \# \smo_{\gbG},$$ where $\gbG = {\cal G}(\partial M^5)$ denotes the regular genus of the boundary $\partial M^5$ and $\smo_{\gbG}$ denotes the connected sum of $h\geq 1$ orientable $5$-dimensional handlebodies $\cmo_{\alpha_i}$ of genus $\alpha_i\geq 0$ ($i=1,\ldots, h$), so that $\sum_{i=1}^h \alpha_i = \gbG.$ \par Moreover, we give the following characterizations of orientable PL $5$-manifolds $M^5$ with boundary satisfying particular conditions related to the ``gap'' between ${\cal G}(M^5)$ and either ${\cal G}(\partial M^5)$ or the rank of their fundamental group $\rk\bigl(\pi_1(M^5)\bigr)$: $$\displaylines{{\cal G}(\partial M^5)= {\cal G}(M^5) = \varrho \Longleftrightarrow M^5 \cong \smo_{\gG}\cr {\cal G}(\partial M^5)= \gbG = {\cal G}(M^5)-1 \Longleftrightarrow M^5 \cong (\bdo) \# \smo_{\gbG}\cr {\cal G}(\partial M^5)= \gbG = {\cal G}(M^5)-2 \Longleftrightarrow M^5 \cong \#_2 (\bdo) \# \smo_{\gbG}\cr {\cal G}(M^5) = \rk\bigl(\pi_1(M^5)\bigr)= \varrho \Longleftrightarrow M^5 \cong \#_{\gG - \gbG}(\bdo) \# \smo_{\gbG}.\cr}$$ \par Further, the paper explains how the above results (together with other known properties of regular genus of PL manifolds) may lead to a combinatorial approach to $3$-dimensional Poincar\'e Conjecture.